Cesium carbonate → HCID 118159840, compound

HRID 628431Notes

Reaction equation

HRID 628431 reaction equation
Cl[C:2]1[N:7]=[C:6]2[CH:8]=[C:9]([C:20]3[O:21][CH:22]=[CH:23][N:24]=3)[N:10]([S:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)(=[O:13])=[O:12])[C:5]2=[CH:4][CH:3]=1.[NH:25]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[NH:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28].C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.C(Cl)Cl.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.NC1C=CC=CC=1C1C=CC=CC=1[Pd]Cl>[O:21]1[CH:22]=[CH:23][N:24]=[C:20]1[C:9]1[N:10]([S:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)(=[O:13])=[O:12])[C:5]2[C:6](=[N:7][C:2]([N:25]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[NH:26][C:27]([O:29][C:30]([CH3:31])([CH3:32])[CH3:33])=[O:28])=[CH:3][CH:4]=2)[CH:8]=1.[O:21]1[CH:22]=[CH:23][N:24]=[C:20]1[C:9]1[NH:10][C:5]2[C:6](=[N:7][C:2]([N:25]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[NH:26][C:27]([O:29][C:30]([CH3:31])([CH3:32])[CH3:33])=[O:28])=[CH:3][CH:4]=2)[CH:8]=1

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 85431Di-tert-butyl bicarbamateHCID 118159922HCID 118159922, compound

Product 2

HCID 118159617HCID 118159617, compoundYield 13%HCID 118159840HCID 118159840, compoundYield 14%

Reagents, catalysts & solvents 3

HCID 178439015HCID 178439015, compoundCatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
140 °C

Procedure

A degassed mixture of 5-chloro-2-(1,3-oxazol-2-yl)-1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyridine (0.80 g, 2.2 mmol, from Step 1), di-tert-butyl hydrazine-1,2-dicarboxylate (1.0 g, 4.4 mmol, Aldrich), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine-(2′-aminobiphenyl-2-yl)(chloro)palladium (1:1) (0.17 g, 0.22 mmol, Aldrich), and Cs2CO3 (1.1 g, 3.3 mmol, Aldrich) in toluene (10. mL) was heated at 140° C. for 2 hours. The mixture was cooled to room temperature, diluted with DCM, filtered and concentrated. Flash chromatography, eluting with a gradient from 0-50% EtOAc in hexanes afforded di-tert-butyl 1-[2-(1,3-oxazol-2-yl)-1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyridin-5-yl]hydrazine-1,2-dicarboxylate (yield: 0.18 g, 14%; LCMS (M+H)+: 556.2) and also di-tert-butyl 1-[2-(1,3-oxazol-2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl]hydrazine-1,2-dicarboxylate (yield: 0.12 g, 13%; LCMS (M+H)+: 416.2). Each of these products was dissolved separately in acetic acid (5.0 mL) and heated in the microwave at 180° C. for 5 minutes. Both reaction mixtures were combined, and the acetic acid was removed in vacuo. The residue thus obtained was dissolved in THF (20 mL) and treated with 2.8 M NaOH in water (10 mL, 28 mmol) for 40 minutes, after which time the reaction mixture was treated with 1 N HCl to achieve pH˜10, and then saturated with solid NaCl. The aqueous solution was extracted with 15% iPrOH in CHCl3. The organic extract was dried over sodium sulfate, filtered and concentrated. The product was purified by flash chromatography, eluting with a gradient from 0-10% MeOH in DCM. Yield: (76 mg, 9%).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. filtrationfiltered
  3. concentrationconcentrated
  4. washFlash chromatography, eluting with a gradient from 0-50% EtOAc in hexanes

Sources & evidence

ORD record
ord-825c11ad1e6e4ef1bacce8c007f90957
Source dataset
uspto-grants-2016_04
Patent number
US09309246B2

Reaction notes

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